Bronchial angiogenesis in severe glucocorticoid-dependent asthma

Abstract

To examine the role of the bronchial microvasculature and adhesion molecule expression in severe asthma, the authors have performed an immunohistochemical study on bronchial biopsies comparing 15 glucocorticoid-dependent asthmatics, 15 mild asthmatics and eight control subjects.Serially cut glycol methacrylate-embedded sections were stained with monoclonal antibodies identifying the vessel marker EN-4, intercellular adhesion molecule (I-CAM)-1, vascular cell adhesion molecule (VCAM)-1, E-and P-selectin. Sections were also stained for lymphocyte function associated antigen (LFA)-1 and very late antigen (VLA)-4.By comparison with mild asthma and nonasthma, severe asthma was characterized by increased numbers of submucosal vessels (p=0.009) which was associated with increased numbers of vessels expressing ICAM-1 (p=0.005). A highly significant correlation was found between the total number of EN-4+ vessels and the vessels expressing ICAM-1 (r=0.85, p=0.01). In contrast, E-selectin expression was lower in severe as compared with mild asthma (p=0.01) but not different from normal. No differences were found between the three groups in the expression of VCAM-1 and Pselectin nor in numbers of LFA-1+ and VLA-4+ cells.The results of this study support the notion that mucosal neovascularization is an important feature of airways remodelling in severe asthma. This is associated with a relatively higher density of vessels expressing intercellular adhesion molecule-1, although the expression of this adhesion molecule per vessel was not raised.

Increased immunoreactivity of stromal cell-derived factor‐1 and angiogenesis in asthma

“…Studies using anti-factor VIII have consistently found fewer vessels, or have not detected any significant differences in vascularity in the airways of asthmatics [2,3]. A recent study by VRUGT et al [19] evaluated blood vessels with EN-4 and found a marked increase in blood vessel number in patients with severe asthma. Many mediators released during inflammation are potentially capable of causing bronchial vascular dilatation.…”

Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: The one airway concept revisited

“…59 Finally, ASM contraction can alter the mechanical properties of the airway wall, promoting mechanotransduction pathways that contribute to remodelling and initiating cascades that synergize with other inflammatory mechanisms. 60 Enhanced vascularity correlates with asthma severity 61 and is a key feature in the airways of people who died from asthma. 62 Changes to the airway vasculature include increased numbers of vessels per unit area with enhanced vessel size and associated vasodilation and leakage leading to mucosal oedema.…”

Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-α

“…Histopathologic analysis of lung and immunohistochemical examination of ICAM-1 and VCAM-1 were performed as previously described (Vrugt et al, 2000). Animals were sacrificed with an overdose of ether at 48 h after the last OVA exposure and histologic specimens were collected.…”

“…Mice lungs were minced and sonicated in Pro-Prep buffer (50 mg/ml) containing 50 mM Tris-Cl, pH 7.5, 1 mM EDTA, 150 mM NaCl, and protease inhibitors using a tip-type sonicator (Branson sonifier, Branson ultrasonics, CT, 20% amplitude, 3 min), followed by centrifugation for 20 min at 1,000 × g. Protein expression levels in cell lysates were analyzed by Western blot analysis, as previously described (Vrugt et al, 2000;Lee et al, 2003). Equal amounts of cell lysate were separated on an SDS polyacrylamide gel under reducing conditions, and were then transferred onto Protran nitrocellulose membranes (Schleicher & Schuell, Keene, NH).…”